Department of Oral and Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China.
Adv Sci (Weinh). 2023 Sep;10(25):e2207549. doi: 10.1002/advs.202207549. Epub 2023 Jul 3.
LncRNAs play a critical role in oral squamous cell carcinoma (OSCC) progression. However, the function and detailed molecular mechanism of most lncRNAs in OSCC are not fully understood. Here, a novel nuclear-localized lncRNA, DUXAP9 (DUXAP9), that is highly expressed in OSCC is identified. A high level of DUXAP9 is positively associated with lymph node metastasis, poor pathological differentiation, advanced clinical stage, worse overall survival, and worse disease-specific survival in OSCC patients. Overexpression of DUXAP9 significantly promotes OSCC cell proliferation, migration, invasion, and xenograft tumor growth and metastasis, and upregulates N-cadherin, Vimentin, Ki67, PCNA, and EZH2 expression and downregulates E-cadherin in vitro and in vivo, whereas knockdown of DUXAP9 remarkably suppresses OSCC cell proliferation, migration, invasion, and xenograft tumor growth in vitro and in vivo in an EZH2-dependent manner. Yin Yang 1 (YY1) is found to activate the transcriptional expression of DUXAP9 in OSCC. Furthermore, DUXAP9 physically interacts with EZH2 and inhibits EZH2 degradation via the suppression of EZH2 phosphorylation, thereby blocking EZH2 translocation from the nucleus to the cytoplasm. Thus, DUXAP9 can serve as a promising target for OSCC therapy.
长链非编码 RNA（lncRNA）在口腔鳞状细胞癌（OSCC）的进展中起着关键作用。然而，大多数 lncRNA 在 OSCC 中的功能和详细分子机制尚未完全阐明。本研究鉴定了一种新型核定位的 lncRNA，即 DUXAP9（DUXAP9），其在 OSCC 中高表达。高水平的 DUXAP9 与 OSCC 患者的淋巴结转移、病理分化差、临床分期较晚、总生存期较差和疾病特异性生存期较差呈正相关。过表达 DUXAP9 可显著促进 OSCC 细胞的增殖、迁移、侵袭和异种移植肿瘤的生长和转移，并上调 N-钙黏蛋白、波形蛋白、Ki67、PCNA 和 EZH2 的表达，下调体外和体内的 E-钙黏蛋白，而敲低 DUXAP9 则以 EZH2 依赖的方式显著抑制 OSCC 细胞的增殖、迁移、侵袭和异种移植肿瘤的生长。发现 Yin Yang 1（YY1）在 OSCC 中激活 DUXAP9 的转录表达。此外，DUXAP9 通过抑制 EZH2 的磷酸化来与 EZH2 相互作用并抑制 EZH2 的降解，从而阻止 EZH2 从核内易位到细胞质。因此，DUXAP9 可以作为 OSCC 治疗的有前途的靶点。
